Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression.
Taken together, all findings here clearly implicated that EGFR-related signal pathways, including EGFR-PI3K-Akt and EGFR-Erk1/2 pathways, were involved in ISO-induced cell growth inhibition and apoptosis in PCa cells, providing a more solid theoretical basis for the application of ISO to treat patients with prostate cancer in clinic.
In summary, our results indicated the distinct roles of 4 PI3K isoforms in the migration of prostate cancer DU145 cells, and they demonstrated the in vitro and in vivo antimetastatic effect of PI3K-isoform specific inhibitors, most of which are in clinical trials.-Zhang, Z., Liu, J., Wang, Y., Tan, X., Zhao, W., Xing, X., Qiu, Y., Wang, R., Jin, M., Fan, G., Zhang, P., Zhong, Y., Kong, D. Phosphatidylinositol 3-kinase β and δ isoforms play key roles in metastasis of prostate cancer DU145 cells.
We find that not only the PI3Kα- and PI3kβ-isoforms, but also PI3Kδ, are associated with the epithelial-mesenchymal transition (EMT), a critical process distinguishing indolent from aggressive prostate cancer.
The p110β isoform of PI3K plays a particularly important role in the pathogenesis of prostate cancer, but the origin of its activation was so far unknown.
In conclusion, the results of the present study indicate that PGE2 significantly upregulated the mRNA and protein expression levels of the MMP‑2, MMP‑9, RANKL and RUNX2, and the EP4 receptor was involved in the cell proliferation and invasion of PCa via the cAMP‑PKA/PI3K‑Akt signaling pathway.
Western blot analysis indicated DT-13 significantly decreased the phosphorylation of PDK1, Akt, mTOR as well as p70S6K, suggesting the pro-apoptotic and anti-metastatic effects of DT-13 on prostate cancer cells might be attributed to the blockade of PI3K/Akt pathway.
Herein we outline the role of the PI3K pathway in prostate cancer and, in particular, its association with androgen receptor signaling in the pathogenesis and evolution of prostate cancer, as well as a review of the clinical utility of PI3K targeting.
These results suggest that coumestrol can inhibit progression of prostate cancer and may be a novel chemotherapeutic agent for treatment of prostate cancer via effects mediated via the PI3K/AKT and ERK1/2 and JNK MAPK cell signaling pathways..
The molecular cause of prostate cancer (PCa) is still unclear; however, its progression involves androgen, PI3K/Akt, and PTEN signaling, as cycle and apoptotic pathways.
Our previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs.
These data argue for AKT-associated HK2-mediated metabolic reprogramming and mitochondrial association in PI3K-driven prostate cancer as one survival mechanism downstream of AR inhibition.